An intact posterior lens capsule is required for implantation of a wide variety of intraocular lenses. A surgical technique that preserves the posterior lens capsule, and which has found use in the treatment of cataracts, is generically termed extracapsular cataract extraction. The technique includes extracapsular cataract extraction, phacoemulsification, endocapsular extraction and intercapsular extraction. Newer methods of extracapsular cataract extraction under development, such as the Kelman phaco fly, would remove a cataract through a puncture of the lens capsule and refill the lens capsule bag with a flexible substance or an inflatable lens to restore vision and to preserve or restore natural accommodation.
Extracapsular cataract extraction is a desirable method for removing cataracts due to a lower incidence of post-operative complications such as cystoid macular edema and possible retinal detachment. However, this surgical method is accompanied by a significant incidence of posterior lens capsule opacification, which may require additional surgical procedures such as posterior capsulotomy or repolishing of the posterior lens capsule to provide good vision. Virtually all pediatric patients and approximately 50% of adult patients undergoing extracapsular cataract extraction develop an opaque secondary cataract within 3 to 5 years.
The pathogenesis of posterior lens capsule opacification after extracapsular cataract extraction is reported to be due to proliferation of remnant lens epithelial cells on the posterior lens capsule to form abortive lens "fibers" and "bladder" cells (i.e., Elschnig's pearls). Various cytotoxic agents are reported to inhibit this secondary cataract formation or posterior lens capsule opacification, including vincristine and vinblastine. Radiation has also been tried and was reported to be promising. Methotrexate and retinoic acid have been reported for instillation in the anterior chamber of the eye to kill residual lens epithelial cells and thus prevent posterior lens capsule opacification. These methods are relatively non-specific and can damage and/or kill other cells in addition to the lens epithelial cells.
Techniques which are designed to more specifically kill lens epithelial cells have included introduction of immunotoxins capable of binding specifically to residual lens epithelial cells on the lens capsule remnant at the time of cataract surgery. These immunotoxins have been shown to inhibit proliferation of lens epithelial cells in vitro. However, the immunotoxin activity is both dose and time dependent and it is difficult to maintain the immunotoxin in the posterior chamber at a concentration and for a time sufficient to prevent proliferation of and/or to kill the residual lens epithelial cells. The immunotoxin passes through the pupil into the anterior chamber where it is lost through normal aqueous outflow. It would therefore be of interest to develop methods and compositions for retarding loss of the immunotoxin from the posterior chamber for use in preventing secondary cataract formation or posterior lens capsule opacification. Such a device would have the advantage of providing a sufficient concentration of immunotoxin in the vicinity of the eye for a time sufficient to kill any lens epithelial cells remaining in the eye after extracapsular extraction.
Relevant Literature
Biodegradable microcapsules for use in the eye are disclosed in Wang (U.S. Pat. No. 4,853,224). An eyeball medication dispensing tablet has been disclosed in U.S. Pat. No. 3,416,530. U.S. Pat. No. 4,526,938 discloses copolymers which can be used to provide for continuous release of polypeptides. See also Heyrman, et al., (1989) J. Cataract Refract. Surg., 15:169-175.
Examples of polymeric delivery systems include Sherwood, et al. (1992) Bio/Technology 10:1446-1449; Hora, et al. (1990) Bio/Technology 8:755-757.
Immunotoxins and their use for treating secondary cataracts are described in U.S. Pat. Nos. 4,871,350 and 4,432,751 and European Patent 0088606. U.S. Pat. No. 4,432,751 also discloses use of a combination of monoclonal antibodies and complement for preventing secondary cataracts. Complement-fixing monoclonal antibodies which bind specifically with lens epithelial cells and have low or no cross-reactivity with other cells found in the anterior segment of the eye are disclosed in U.S. Pat. No. 5,202,252. The use of sugars such as trehalose to prepare antibodies for storage is described in Rowser (U.S. Pat. No.4,891,319).